Aspergillus
species

The
U.S. Government's Occupational Safety and Health Administration [OSHA] lists
the following Aspergillus species as all being
allergens and irritants and a cause
of Hypersensitivity pneumonitis and Dermatitis: Aspergillus flavipes, Aspergillus flavus, Aspergillus fumigatus,
Aspergillus glaucus, Aspergillus nidulans, Aspergillus niger,
Aspergillus ochraceus, and Aspergillus versicolor.

Recognized by its distinct conidiophores terminated by a swollen vesicle
bearing flask-shaped phialides. The phialides may be borne directly on
the vesicle (a) or on intervening metulae (b). Some species may form
masses of thick-walled cells called "hülle cells" (c). The spores come
in several colours, depending upon the species, and are produced in long
chains from the ends of the phialides. Commonly isolated from soil,
plant debris, and house dust; sometimes pathogenic to man. Holomorphs:
Emericella,
Eurotium,
Neosartorya, and others. Refs: Raper and Fennell 1965; Samson 1979.

Aspergillusspecies is
cosmopolitan, filamentous, saprobic fungus. It is widely distributed in
nature. It is primarily isolated from soils, especially cultivated
soils, decomposing plant material, and indoor air environment.

Species

There are around one
hundred eighty – five species under the genus Aspergillus.
Around twenty species have been reported so far as causative agents of
opportunistic infections in humans. Among these, Aspergillus
fumigatus is the most frequently isolated species, followed by
Aspergillus flavus and Aspergillus niger.
Among the other species not often isolated as opportunistic pathogens
are Aspergillus clavatus, Aspergillus glaucus group,
Aspergillus nidulans, Aspergillus oryzae, Aspergillus
terreus, Aspergillus ustus and Aspergillus versicolor.

Aspergillus flavus

Culture of Aspergillus flavus.

Conidial head of A. flavus.
Note: conidial heads with both uniseriate and biseriate arrangement of
phialides may be present.

Clinical Significance of Aspergillus flavus

Aspergillus
flavus has a world-wide distribution and normally occurs as a
saprophyte in soil and on many kinds of decaying organic matter. A.
flavus is the second most common species (next to A. fumigatus)
to be isolated from human infections, and it is often associated with
invasive aspergillosis seen in immunosuppressed patients and in
paranasal sinus infections.

Conidial head of
A. fumigatus
(Note: uniseriate row of phialides on
the upper two thirds of the vesicle)

Clinical Significance ofAspergillus fumigatus

Based on the research conducted by the
National Center for Biotechnology Information (NCBI),
Aspergillus fumigatus can also cause allergic bronchopulmonary and
sinus infections. Patients with asthma and cystic fibrosis can
frequently develop allergic broncho-pulmonary aspergillosis (ABPA), a
hypersensitivity reaction to the fungus
Aspergillus fumigatus, which frequently leads to a progressive loss
in lung function. Morever, in developing countries patients with
compromised immune response can develop keratitis, which usually leads
to unilateral blindness.

Aspergillus
species are recognized to play a significant role in three different
clinical settings in man namely, in opportunistic infections, allergic
conditions, and in toxicoses. The major factor which led to the emergence
of opportunistic infections is immunosuppression. Opportunistic infections
are generally called aspergillosis. The most common forms of aspergillosis
in humans are pulmonary in nature; on the other hand, other deep infections
are also encountered particularly among immunocompromised patients. Among
all filamentous fungi, Aspergillus is generally the most recovered
one in invasive infections and is second to Candida as the most
frequently isolated fungus in opportunistic mycoses.

Furthermore, there
are numerous outbreaks of disseminated aspergillosis cases that have been
recorded in neutropenic patients in concurrence with construction /
renovation projects in hospital environments.

Some Aspergillus species
produce various mycotoxins which have proven to possess carcinogenic
potential particularly in animals and these are acquired through chronic
ingestion. Aspergillus flavus produces aflatoxin which is a well – known
mycotoxin. Aflatoxin may induce hepatocellular carcinoma and it contaminates
foodstuffs such as peanuts and grains. Ingestion of high amounts of
aflatoxin may induce toxic effects in poultry animals fed with aflatoxin –
contaminated grain.

Aspergillus
species are known as occasional causative agent of respiratory infection in
birds and mycotic abortion in certain animals, particularly cattle and
sheep.

Aspergillus
species are also encountered as common laboratory contaminants due to being
ubiquitous in nature.

Other Health
Effects of Aspergillus mold

Aspergillosis. Although metabolites of species of Aspergillus
(Hyphomycetes) cause other health problems, such as acute and chronic
aflatoxin poisoning, we are concerned here only with diseases caused by
the growth of the fungus itself somewhere in the body.

(1)
Bronchopulmonary aspergillosis is usually caused by Aspergillus
fumigatus, which colonizes mucus within the bronchi, evoking a severe
allergic reaction.

(2) In
Aspergilloma, the fungus forms a mycelial ball in a lung cavity
produced by an earlier attack of tuberculosis. The wall of the cavity may
erode, causing the patient to spit blood, and necessitating surgical
intervention.

(3) Invasive
aspergillosis is found only in patients who are severely debilitated,
or are immunosuppressed, as in AIDS. The fungus grows outward from the
lung, invading blood vessels and spreading to other organs through the
bloodstream. This insidious disease is usually fatal, and is often
diagnosed only when an autopsy is performed. [from Bryce Kendrick's The
Fifth Kingdom]

Macroscopic Features

ØThe
major macroscopic characteristics that are essential in Aspergillus
species identification are the growth rate, colony color and thermo –
tolerance;

Ø
Texture of colonies varies from being downy to powdery;

ØThe
growth rate varies from slow to rapid depending on the species with diameter
size ranging from 0.5 to 1 cm and 1 to 9 cm for Aspergillus species
with slow growth and with moderately to rapid growth, respectively, after
seven days of incubation at 25°C on Czapek – Dox agar;

Ø
Surface colony color may also vary depending on the species while the
reverse is mostly uncolored to pale yellow, however, some strains of
Aspergillus nidulans may be purple or olive while it is orange to purple
in Aspergillus versicolor;

ØThe
only thermo – tolerant Aspergillus which can grow at temperature
range of 20°C to 50°C is Aspergillus fumigatus.

Microscopic
Features

ØHyphae are
septate and hyaline; and

Ø
Conidiophores arise from the basal foot cell found at the supporting hyphae
and terminate in a vesicle at the tip;

Ø
Vesicle is the typically formation for the genus Aspergillus;

Ø
Phialides are flask – shaped, may either cover the surface of the vesicle
entirely called as “radiate head,” or partially at the upper surface only
termed as “columnar head,” and may either be uniseriate – directly attached
to the vesicle, or biseriate – attached to the vesicle via a supporting
cell, metula;

Ø
Conidia are found over the phialides forming radial chains and with diameter
size of 2 to 5 µm.

ØOther
microscopic structures of the genus Aspergillus are:

a.
Aleuriconidia – observed with a truncated base and carries remnants of the
lysed supporting cell; a type of conidium produced by lysis of the cell that
supports it;

b.
Cleistothecia – produced during the sexual production of some
Aspergillus species, are round and closed structures which enclose the
ascospore – containing asci wherein the asci are distributed into the
surrounding upon the bursting of cleistothecia;

c. Hülle
cells - are large sterile cell bearing a small lumen; and

d.
Sclerotia - are compact or hard masses of mycelium.

Table 1.
Morphological Characteristics of Aspergillus species

Aspergillus
species

Colony
Color

Conidial
Head

Conidiophore

Phialides

Other
Characteristics

Surface

Reverse

Aspergillus flavus

Yellow-green

Yellow, brownish

Mostly radiate, some becoming columnar at maturity

Rough, colorless

Uniseriate and biseriate

Sclerotia occasionally present

A. fumigatus

Gray green, blue green

yellowish

Columnar

Smooth, colorless or greenish

Uniseriate

Good growth at 480C

A. glaucus group

Green and yellow

Yellowish, brown

Radiate to loosely columnar

Smooth, colorless

Uniseriate

Yellow to orange cleistothecia present

A. nidulans

Green, buff

Purplish red, olive

Short columnar

Smooth, brown

Biseriate

Round hülle cells and red cleistothecia usually present

A. niger

Black

White, yellowish

Radiate, however, becoming loosely columnar at maturity

Smooth, colorless or brown

Biseriate

-

A. terreus

Brown, cinnamon

Yellowish brown

Columnar

Smooth, colorless

Biseriate

Round, solitary, aleurioconidia
produced directly on hyphae

A. versicolor

White, buff, yellow, pink, pale green

White, yellow, purplish red

Radiate

Smooth, colorless

Biseriate

Round hülle cells occasionally present

Laboratory Precautions

General laboratory
precautions are required, no special safety measures needed.

Susceptibility

Most of
Aspergillus isolates yield acceptably low MICs for amphotericin B,
itraconazole and voriconazole, however, a number of isolates show high
MICs which indicates potential prediction of resistance. Such as the few
isolates of Aspergillus fumigatus which are itraconazole –
resistant and Aspergillus terreus resistant to amphotericin B.
Fortunately, voriconazole appears effective in vitro against
itraconazole – resistant Aspergillus fumigatus.

Treatment of
invasive aspergillosis is still troublesome with high rate of mortality.
The clinical success rate of both amphotericin B and itraconazole are still
unsatisfactory due to low efficacy and / or high toxicity of the drugs and
existence of adverse immune status of the host.

The novel azoles
which include voriconazole, posaconazole or ravuconazole, glucan inhibitors
such as caspofungin and V - echinocandins, and liposomal nystatin are active
in vitro against Aspergillus and remain promising for future
therapy treatment of aspergillosis.